A novel holder and microfluidic system for spatially controlled hypoxia induction, mechanical stimulation and cardiac regeneration research.

Over the years, cardiovascular diseases have remained a leading cause of mortality worldwide, necessitating advanced experimental models to mimic the natural environment of the heart as closely as possible. New microfluidic heart models would enable precise modelling of the healthy heart as well as pathological mechanisms occurring during cardiac ischemia and testing new therapies would become more accessible than it is currently. In this study, we developed a two layer holder for creating hypoxic conditions in a dedicated microfluidic system for modelling cardiac infarction. By integrating the holder with a microsystem utilizing nanofibrous mats with iron(II, III) oxide (Fe3O4) magnetic nanoparticles we were able to create a tool for using (potentially patient specific) induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in cardiac research. In the microsystem we induced hypoxia and conducted preliminary observations of cardiac regeneration using induced pluripotent stem cells (iPSCs). We found that iPSCs express cTnT when co-cultured with hypoxia-damaged iPSC-CMs indicating that the holder with an integrated microsystem can be used for hypoxia and cardiac regeneration studies.